Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.,ACS Chemical Biology

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Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-07-18 , DOI: 10.1021/acschembio.8b00463
Victor Vitvitsky ₁ , Jan Lj Miljkovic _{2,

3} , Trever Bostelaar ₁ , Bikash Adhikari _{2,

3} , Pramod K Yadav ₁ , Andrea K Steiger ₄ , Roberta Torregrossa ₅ , Michael D Pluth ₄ , Matthew Whiteman ₅ , Ruma Banerjee ₁ , Milos R Filipovic _{2,

3}

Affiliation

Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by H2S exhibits hysteretic behavior, which suggests the involvement of reactive sulfur species in the reduction process and is consistent with a reaction stoichiometry of 1.5 mol of Cyt C reduced/mol of H2S oxidized. H2S increases O2 consumption by human cells (HT29 and HepG2) treated with the complex III inhibitor antimycin A, which is consistent with the entry of sulfide-derived electrons at the level of complex IV. Cyt C-dependent H2S oxidation stimulated protein persulfidation in vitro, while silencing of Cyt C expression decreased mitochondrial protein persulfidation in a cell culture. Cyt C released during apoptosis was correlated with persulfidation of procaspase 9 and with loss of its activity. These results reveal a potential role for the electron transfer chain in general, and Cyt C in particular, for potentiating sulfide-based signaling.

中文翻译：

H2S 还原细胞色素 c 增强硫化物信号传导。

硫化氢 (H2S) 是一种内源产生的气体，高浓度时有毒。它通过专用的线粒体硫化物氧化途径消除，该途径连接到复合体 III 水平的电子传递链。先前已报道过 H2S 直接还原细胞色素 c (Cyt C)，但尚未对其进行表征。在本研究中，我们证明 H2S 还原铁 Cyt C 表现出滞后行为，这表明还原过程中涉及活性硫物质，并且与 1.5 mol Cyt C 还原/mol H2S 氧化的反应化学计量一致。 H2S 增加了用复合物 III 抑制剂抗霉素 A 处理的人体细胞（HT29 和 HepG2）的 O2 消耗，这与硫化物衍生电子在复合物 IV 水平的进入一致。 Cyt C 依赖性 H2S 氧化刺激了体外蛋白质过硫化，而 Cyt C 表达沉默则减少了细胞培养物中线粒体蛋白质过硫化。细胞凋亡过程中释放的 Cyt C 与 procaspase 9 的过硫化及其活性丧失相关。这些结果揭示了电子传递链（特别是 Cyt C）在增强基于硫化物的信号传导方面的潜在作用。

更新日期：2018-07-02

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